Inner ear anatomy and surrounding structures. Endolymph (orange) fills the membranous labyrinth that is suspended within the bony labyrinth, cushioned by surrounding perilymph (pink). Right ear from an inferior oblique view (see skull orientation) to demonstrate the cochlear and vestibular aqueducts. © Corrie Roehm
Inner Ear Infections
Infections affecting the inner ear can be classified as primary (infections that intrinsically involve the inner ear), or secondary (infections that affect the inner ear by extension from contiguous anatomic structures) (Table 5.1). Pathogens can reach the inner ear by multiple routes, including hematogenously, via the meninges, through anatomic connections in the temporal bone between the cerebrospinal fluid and the inner ear (cochlear duct, vestibular aqueduct), from the middle ear through the oval or round window, or through abnormal congenital or acquired dehiscence of the otic capsule . Vertical infections include maternal to fetal transmission of pathogens across the placental membranes, resulting in congenital infections. Pathogens can also enter the inner ear through colonization of intracochlear implants , particularly in now-discontinued implant models utilizing an intracochlear spacer or electrode positioner . Cochlear implants are increasingly used in pediatrics for the treatment of severe to profound sensorineural hearing loss and can become secondarily infected, introducing infection into the inner ear along the intracochlear electrode through surgical openings into the cochlea including the round window membrane or a cochleostomy. A study conducted to describe the microbial flora associated with infected and non-infected cochlear implants, based on indication for removal, found all tested implants to have evidence of microbes . The bacterial species involved was different depending on whether the indication for removal was infection or another cause. Staphylococcus aureus was more commonly isolated from infected cochlear implants. Biofilm formation has also been recognized as a cause of cochlear implant failures, even when infection was not the indication for implant removal .
Organisms associated with inner ear infections
Conditions associated with primary inner ear infections
Conditions associated with secondary inner ear infections
Middle ear infections
Infectious agents associated with primary infections
Infectious agents associated with secondary infections
Haemophilus influenza type b
Group A streptococcus
Herpes virus simplex/Varicella zoster
Parvovirus B 19
Etiologies of Primary Inner Ear Infections
CMV belongs to the family of the herpesvirus group and it can remain latent in tissues after initial infection. The route of acquisition of CMV infection includes horizontal transmission (person to person), via the respiratory tract, urinary, genital tract or contact with infected bodily fluids, or by transfusion of CMV infected blood products; and vertical transmission (mother to infant). Vertical transmission can result in congenital infection, which can be associated with hearing loss.
Vertical transmission can occur at any time during pregnancy or at the time of birth. Vertical transmission occurs in about 30 % of infected mothers, but not all fetuses are affected. Congenital CMV infection occurs in about 1 % of all live-born infants and the majority of infected neonates appear healthy at birth. Symptomatic congenital infection can be acquired at any time during pregnancy, but congenital infection with severe sequalae is most likely associated with primary maternal infection in the first half of pregnancy.
Horizontally acquired CMV infection, even in neonates, can be symptomatic affecting multiple organ systems, but it is not associated with hearing loss.
Congenital CMV infection is the leading cause of sensorineural hearing loss .
Hearing loss can be present at birth and diagnosed with universal newborn hearing screening, or it can develop months to years later. The hearing loss is typically progressive through childhood. The deficit can be unilateral or bilateral, with bilateral hearing loss developing in 37 % of congenitally infected symptomatic infants . Congenital CMV hearing loss involves cochlear damage primarily in the scala media and the marginal cell layer of the stria vascularis, with associated generalized inflammation in the organ of Corti, the cochlear nerve and spiral ganglia . In a study of human fetuses at 21 weeks gestation with known CMV infection, virus was isolated from the inner ear fluid in 45 % of the fetuses studied, and in more than half both inner ears were infected with multiple structures involved . A recent study of 76 pediatric patient receiving cochlear implants, found that more than 14 % were due to CMV. Perilymph fluid obtained at the time of implant placement, was compared to CMV from dried blood spots, and in one case of congenital CMV infection, viral strains were found to be genotypically identical . The onset of progressive hearing loss usually occurs during the preschool years. But this decline in hearing has also been observed in school age children with congenital CMV. This finding underlies the importance of early diagnosis of CMV infection and possibility of offering close audiologic evaluation for congenitally infected neonates. Evidence of disseminated infection at birth (petechial, thrombocytopenia, intrauterine growth retardation, hepatitis or hepatosplenomegaly) is predictive of hearing loss, with about a third to half of children with symptomatic CMV infection developing hearing loss .
Diagnosis of congenital CMV infection is by definition confirmed within the first 3 weeks of life. Viral culture of the urine evaluating for CMV is a non-invasive standard diagnostic approach, and should be considered in neonates that are found to have abnormal hearing tests . CMV detection by PCR technology of blood or cerebrospinal fluid has become readily available in commercial laboratories and can also be used for diagnosis. An approach for diagnosis of asymptomatic congenitally infected neonates needs to be standardized. Neonates with hearing loss, should be evaluated by an otorhinolaryngologists and tested for CMV infection. If CMV testing is positive, referral to a pediatric infectious disease specialist is recommended for further evaluation and treatment.
Regarding therapeutic approaches for congenital CMV infection, ganciclovir has been used for the past several decades. A randomized controlled trial using ganciclovir intravenously for 6 weeks in neonates with symptomatic CMV infection, involving the central nervous system showed hearing improvement or maintenance of normal hearing in about 80 % of the infant treated at 6 month follow up . Development of neutropenia is common during therapy as well as liver enzyme abnormalities, and these should be monitored.
A study evaluating the use of prolonged (6 months) oral valganciclovir in symptomatic infants with congenital CMV has shown that language and receptive communication scores were superior in the group of infants receiving 6 months of oral valganciclovir with normal hearing also more likely to occur at 6 month follow up (46 % vs. 56 %), 12 month follow up (50 % vs. 65 %) and 24 month follow up (60 % vs. 68 %) . A similar study in Europe has shown promising results .
A therapeutic dilemma remains in otherwise well appearing neonates who are found to have hearing loss and test positive for CMV, but have no radiologic evidence of CNS involvement. There may be a role for oral valganciclovir in this population.
Rubella virus is a positive-stranded RNA virus. It belongs to the Togaviridae family. Maternal infection can result in congenital rubella syndrome. Fetal involvement earlier in pregnancy results in a higher incidence of congenital defects. Infection occurring during the third trimester of pregnancy results more commonly in deafness and retinopathy. The association between congenital rubella and deafness was first recognized in the 1940s and the virus has been shown to infect the inner ear .
Hearing is affected in 68–93 % of infected infants. As seen with CMV infection, hearing loss can be unilateral or bilateral and progressive ([19, 20]).
The diagnosis should be suspected when there is maternal history of infection during pregnancy or if the infant presents with clinical manifestations compatible with congenital rubella syndrome, including cataracts, congenital heart disease, hearing impairment, pigmentary retinopathy, microcephaly and developmental delay. The risk of congenital infection and defects is highest during the first 12 weeks of pregnancy, and decreases after the 12th week, with rare defects after the 20th week of gestation . Serology testing with rubella IgM can provide information, but with higher risk of false positive compared to culture results . The virus can be isolated in culture, up to 1 year after infection in specimens from throat, urine, blood and CSF.
There is no antiviral therapy available for congenital rubella infection. The most important preventive measure is maternal vaccination against rubella. Routine rubella immunization as part of the MMR, is recommended at 12–15 months of age, with a second dose prior to school entry at 4–6 years. Rubella vaccine should not be given to pregnant women or to those women considering pregnancy within 3 months of vaccine, but women that are found to be rubella non-immune should be vaccinated at the time of delivery.
Mumps virus is an enveloped negative-stranded RNA virus, and it belongs to the Paramyxoviridae family. Infection with this virus is acquired via contact with infected respiratory secretions. After local viral replication in the nasopharyngeal region, there is a phase of viremia that allows the mumps virus to infect the central nervous system, salivary glandular tissue and testis most commonly. Although involvement of the inner ear is not frequently reported, association of mumps infection with hearing loss is well recognized . Hearing loss is usually unilateral and in most cases reversible.
The association of mumps inner ear infection as the cause of hearing loss was reported in a 26 year with prior history of otosclerosis who 2 years after successful stapedectomy, developed mumps and subsequent unilateral hearing loss. At the time of surgical exploration to rule out complications from the otosclerosis process or a perilymph fistula, culture of the perilymph was positive for mumps .
Mumps is suspected in patients with parotitis and it can be confirmed using serology (presence of positive IgM or rising IgG levels). Viral culture, in special media for mumps, from pharynx, CSF or urine can also be performed. PCR is also available from the Centers for Disease Control and Prevention or commercial laboratories of buccal or oral swabs.
There is no specific antiviral therapy against this infection. Vaccination remains the most important tool for prevention. Two doses of mumps vaccine, as part of the MMR, are recommended at 12–15 months and 4–6 years of age.
Measles (Rubeola ) belongs to the Paramyxoviridae family and it is formed by a single-stranded negative-sense RNA genome. After the incubation period (8–12 days), infected patients develop fever, hacking cough, conjunctivitis (nonpurulent), and coryza. Within 48–72 h, Koplik spots develop, and a generalized rash usually appears at the peak of respiratory symptoms.
The most common complication in pediatric patients infected with measles is acute otitis media, but hearing loss is not a frequent event. Measles was reported to be the cause of hearing loss in 13 % of African children with hearing impairment of known etiology .
Pathologic changes of the temporal bone with associated severe necrotizing otitis media has been reported in four fatal cases of measles infection. Half of the patients had inner ear changes, similar to those seen in congenital rubella syndrome .
Severe hearing loss after measles vaccination has been reported and it is usually associated with encephalitis . These cases are rare and should not have a negative impact on recommendations regarding vaccination.
Measles is diagnosed in patients with compatible clinical presentation. Serologic testing can help confirm the diagnosis. Increasing IgM levels, when comparing acute and convalescent serum, indicate recent infection. Culture of this virus is difficult, and serology is the recommended diagnostic tool.
No specific antiviral therapy exists. Vaccination is effective in preventing disease development.
Syphilis is caused by Treponema pallidum. Congenital infection is acquired by the infant from an infected mother, via the placenta. Transmission to the fetus can occur in any stage of syphilitic infection.
Clinical complications of congenital syphilis develop later in life, including sensorineural hearing loss (related to osteochondritis of otic capsule and cochlear architecture degeneration), keratitis and Hutchinson’s teeth. Eighth nerve deafness often starts with high frequency hearing loss when the child is between 8 and 10 years of age . Hearing loss is usually bilateral and it can fluctuate. Meniere’s disease can also develop as a consequence of syphilis infection. Otosyphilis has been associated with development of endolymphatic hydrops. Temporal bone changes including microgummata, bone reabsorption, or new bone formation have been described in specimens belonging to patients with proven syphilis . Literature from the 1960s describes a group of patients treated with steroids, showing improvement in more than 50 %. Patients were treated with penicillin at the time of diagnosis, if they had never received therapy . A case report of bilateral deafness associated with acquired syphilis, non-primary, showed that medical therapy restored unilateral hearing . Other studies have shown variable response to antibiotics and steroids .
Screening for syphilis during early pregnancy, and providing antibiotic treatment to infected mothers, is the best preventive measure against congenital syphilis. Women should be retested at the time of delivery.
In patients that present with sensorineural hearing loss of unknown etiology, luetic, or syphilitic, inner ear disease should be included in the differential diagnosis. If serologic tests as nontreponemal (RPR or VDRL) confirmed by treponemal tests (MHATP or AFT-ABS) are found to be positive, the patient should receive steroids and antibiotics . Penicillin remains the drug of choice, and in cases of otosyphilis, the same regimen used for treatment of neurosyphilis is recommended: Intravenous Aqueous Crystalline Penicillin G for 14 days .
Toxoplasma gondii is an intracellular protozoan parasite and it the cause of toxoplasmosis. Infection occurs when bradyzoites are ingested, during laboratory accidents, via blood transfusion or organ transplantation with infected specimens of tissue or transplacentally. If a pregnant woman acquires the infection early in pregnancy, fetal tissue necrosis usually occurs and affects many tissues, including brain and eye. If the infection is acquired later in pregnancy, the fetus is less severely affected.
Delayed onset, or progressive, hearing loss is reported in up 26 % of in utero acquired toxoplasmosis cases, and those children should undergo audiologic follow up. The incidence of hearing loss correlates with incomplete treatment or lack of treatment for congenitally acquired toxoplasmosis . None of the children that received complete therapy, consisting of 12 months of antiparasitic treatment with Pyrimethamine, Sulfadiazine and Leucovorin, and before they were 2½ years old, developed hearing loss . Audiologic re-evaluation is recommended at 24–30 months of age. For those children with incomplete or no treatment, audiologic evaluation should be performed yearly, until they can reliably complete behavioral audiologic testing .
In a histopathology study of temporal bones of nine newborns who died from congenital toxoplasmosis, 37 % had free or encysted organisms in the temporal bone, and in two of those infants numerous encysted organisms were found inside the inner ear without evidence of tissue necrosis or an inflammatory response. Cystic forms are not associated with an inflammatory response. Hearing loss may be secondary to delayed reactivation of the cystic form to the active tachyzoite, which could be prevented by treatment . Serologic and molecular diagnostic testing in suspected cases of congenital toxoplasmosis should be performed at reference laboratories, and includes testing of blood and CSF. Treatment of congenitally-acquired toxoplasmosis requires combination therapy of one year duration to have a positive impact on hearing outcomes [37–39].
Herpes Virus Simplex (HSV)
HSV type 1 and 2 has been implicated in cases of sudden, sensorineural hearing loss in children. As with many other herpes viruses, three mechanisms of involvement have been postulated. The first is direct invasion of the cochlea or cochlear nerve. Second, reactivation of the virus in the inner ear can cause cellular inflammatory changes. Lastly, an immune response in the inner ear can be precipitated by distant HSV infection. Direct inoculation of HSV into the inner ear of guinea pigs results in similar pathologic changes to those seen in the temporal bone of adults with sudden hearing loss . However, sudden onset of hearing loss appears to be multifactorial, and not only attributable to viral infections like HSV .
The evaluation of sudden sensorineural hearing loss should include serum HSV 1 and 2 PCR as well as serologic evaluation for HSV1 and 2 (IgM and IgG) that could demonstrate seroconversion.
The drug of choice for the treatment of HSV infections is acyclovir. In older children, if there is no evidence of clinical encephalitis, oral therapy with valacyclovir can be considered.
This small, non-enveloped DNA virus is the cause of erythema infectiosum or fifth disease. It is transmitted person to person and humans are its only host. Symptoms involving the inner ear are uncommon. Case reports have described adults presenting with dizziness and hearing difficulties, but the mechanism of involvement is unknown. It is possible that an autoimmune process is ultimately the cause .
Parvovirus B-19 infection can be diagnosed using serologic testing (IgM and IgG) or molecular testing including PCR of the blood.
There is no antiviral therapy effective against parvovirus, but if hearing loss is related to an autoimmune response, the use of immunotherapy (intravenous immunoglobulin) can be of benefit.
There have been a few reported cases of sensorineural hearing loss associated with Mycoplasma pneumoniae infection. In some cases hearing loss has been bilateral, and in all cases occurred early in the course of infection. About half of the patients recovered hearing capacity after receiving treatment with a macrolide. Some patients were also treated with steroids . The diagnosis of these cases was made with the use of antibody testing against mycoplasma . However, the diagnosis of mycoplasma infection can be challenging as serology and polymerase chain reaction do not differentiate infection from asymptomatic colonization. Testing of acute and convalescent paired serum, showing a fourfold increase in titer indicates infection.
Primary Inner Ear Infections
Vestibular neuritis describes inflammation of the inner ear and specifically the vestibular nerve, causing an acute onset of vertigo with imbalance, and possible nausea or vomiting, but with no associated hearing loss. Other clinical synonyms include vestibular paralysis, acute labyrinthitis, vestibular neuropathy and vestibular ganglionitis. The acute phase of symptoms in vestibular neuritis lasts from several hours to several days, with abrupt onset of severe and continuous vertigo, and mild imbalance that can persist for several weeks after an episode. Specific clinical signs include continuous vertigo worsened with head movement, spontaneous nystagmus, reduced or absent responses on caloric testing, and autonomic symptoms like clammy skin, fatigue and pallor . The timeline of vertigo lasting over several hours to days suggests vestibular neuritis instead of other causes of peripheral vertigo with shorter or longer vertiginous episodes.
The infectious causes of vestibular neuritis have not been clearly identified. However, the presence of a preceding viral upper respiratory infection suggests a viral etiology, with previous studies isolating HSV DNA [44, 45]. Borrelia burgdorferi, the cause of Lyme disease, has also been implicated . The differential diagnosis of vestibular neuritis includes other peripheral vestibular disorders like Meniere’s disease, vestibular atelectasia, complications of chronic middle ear disease like labyrinthine fistula or cerebellar abscess , and perilymph fistulas, as well as central issues including vertebrobasilar insufficiency or early anterior inferior cerebellar artery infarction, Wallenberg’s syndrome, migraine-associated vertigo, presyncopal dizziness, paraneoplastic syndrome, drug-induced vertigo, immune-mediated inner ear disorder , multiple sclerosis, or skull base tumors.
The diagnosis of vestibular neuritis primarily rests on a thorough history, including the timeline of vertigo symptoms, and a physical exam evaluating the ear, cranial nerves, tuning fork testing, cerebellar and gait testing, a head thrust test, and a neurological examination. Differentiation between central and peripheral vertigo can be made clinically by evaluating the direction and type of nystagmus, a head-thrust test, and a full neurologic assessment for any associated abnormalities. Peripheral vestibular disorders will produce a mixed horizontal and rotational nystagmus that does not change direction with changes in gaze position, while central nystagmus is typically purely vertical, horizontal or rotational and changes fast-twitch direction with gaze shift . Nystagmus in vestibular neuritis typically is horizontal, rotary and spontaneous, with fast phase away from the involved ear and is reduced with fixation. Head thrust testing can demonstrate vestibular function differences between the ears by stimulating the horizontal vestibuloocular reflex (VOR). Typically, vestibular neuritis is unilateral, and loss of one labyrinth’s function causes a positive head thrust test, while central lesions causing vertigo would have a negative (normal) head thrust test. However, patients with lateral pontine and cerebellar strokes can rarely have a positive head thrust test, and any vascular risk factors or associated clinical features should be carefully considered before excluding central lesions . Formal vestibular testing can be considered with caloric testing or video nystagmography, although this may be difficult to obtain in the acute setting. Vestibular evoked myogenic potential (VEMP) testing can isolate the affected vestibular nerve to the inferior vestibular nerve through the cervical VEMP (cVEMP) that assesses the sacculocollic reflex, or the superior vestibular nerve through ocular VEMP (oVEMP) that assesses the crossed vestibuloocular reflex . Imaging is not often needed, but can be considered based on the history and examination, with contrast tomography (CT) of the temporal bone to evaluate trauma or chronic ear disease, or magnetic resonance imaging (MRI) being preferred to further evaluate any neurologic abnormalities on physical exam. Treatment of vestibular neuritis is primarily supportive, with antiemetics and intravenous hydration if needed, and vestibular suppressants during the acute phase. Steroid use has been studied, with relative benefit to placebo or antiviral treatment , primarily by accelerating the return of normal vestibular function, although this is controversial, and steroid use does not clearly improve long-term outcome . Some studies recommended initiating steroids for patients presenting within 3 days of symptom onset without risk factors for steroid complications, and to use vestibular suppressants and antiemetics only briefly for the first several days to avoid impeding central vestibular compensation in the subacute phase and prolonging symptoms . After the acute phase, vestibular rehabilitation is useful to improve central compensation as the vestibular function slowly returns. Temporal bone pathology in vestibular neuritis has not been frequently reported, in part because the clinical course of the disease is benign and short-lived. Limited available histological data from several studies  showed atrophy of the superior division of the vestibular nerve, with partial or total neuronal loss, and atrophy of the corresponding horizontal and superior ampullae and cristae hair cells. Temporal bone histologic evaluation of the anatomic differences between the inferior/singular and superior vestibular nerves  demonstrated that the bony canal of the superior vestibular nerve and its corresponding arteriole is longer and narrower than the singular nerve, increasing the risk of neural edema causing entrapment and potential ischemia.
Labyrinthitis is a peripheral vestibulopathy clinically characterized by an acute onset of vertigo, often with nausea and vomiting as seen in vestibular neuritis, but in contrast to vestibular neuritis also involves an associated hearing loss. Labyrinthitis can be serous, or purulent, or a “toxic” labyrinthitis caused by inflammation from bacterial or fungal toxins or inflammatory cell mediators entering the inner ear without direct labyrinthine infection . Hearing loss occurs in labyrinthitis with panlabyrinthine inflammation involving the cochlea. Clinical synonyms of labyrinthitis include acute labyrinthitis, acute vestibular neuropathy, viral neurolabyrinthitis, vestibular neuronitis, and vestibular neurolabyrinthitis. Labyrinthitis presents acutely with vertigo, nausea and possible vomiting, hearing loss and difficulty ambulating and vision changes or blurring due to persistent spontaneous nystagmus. These symptoms worsen over several hours, peaking within 1–2 days and resolving gradually over several weeks with a benign course, usually recovering normal vestibular function completely within 1–3 months, although persisting dysfunction is possible, particularly in older patients. Hearing loss can be minimal or not present, or can be severe, and has variable recovery depending on the severity and etiology of the labyrinthitis. A preceding mild upper respiratory or viral illness often occurs 1–2 weeks before the onset of labyrinthitis symptoms. On examination, a full otologic and neurologic examination will typically show normal otoscopic findings and neurologic functioning aside from the peripheral vestibular findings. Patients will often present with nausea or vomiting and nystagmus during the acute phase, and possibly a mild positional vertigo component worsening with head movement. Head thrust testing in acute labyrinthitis may be positive if asymmetric labyrinth involvement is present and causing an imbalance of vestibular function between the ears, as in vestibular neuritis. Further formal vestibular testing can be considered with caloric testing, along with tuning fork and audiometric testing if hearing loss is present. Imaging is typically not necessary, but may be useful for patients with clinical features consistent with other differential diagnoses, including intracranial infection or masses, stroke or temporal bone masses or trauma. The differential diagnosis in labyrinthitis includes ischemic acute labyrinthitis, labyrinthine fistula, cholesteatoma or other erosive temporal bone mass, temporal bone trauma, benign positional vertigo, Meniere’s disease, drug-induced vertigo, acoustic neuroma, or vertebrobasilar stroke. Infectious etiologies suspected in labyrinthitis include viruses (HSV-1 , mumps, measles), bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, Borrelia burgdorferi and Treponema pallidum and other organisms including fungal species [54, 55]. Other potential causes include immune mediated inner ear disease  and microvascular ischemic labyrinthine damage.